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dc.contributor.author | Arriaga, Maria B. | |
dc.contributor.author | Karim, F. | |
dc.contributor.author | Queiroz, A.T.L. | |
dc.contributor.author | Araújo-Pereira, M. | |
dc.contributor.author | Barreto-Duarte, B. | |
dc.contributor.author | Sales, C. | |
dc.contributor.author | Moosa, M.-Y.S. | |
dc.contributor.author | Mazibuko, M. | |
dc.contributor.author | Milne, G.L. | |
dc.contributor.author | Maruri, F. | |
dc.contributor.author | Serezani, C.H. | |
dc.contributor.author | Koethe, J.R. | |
dc.contributor.author | Figueiredo, M.C. | |
dc.contributor.author | Kritski, A.L. | |
dc.contributor.author | Cordeiro-Santos, M. | |
dc.contributor.author | Rolla, V.C. | |
dc.contributor.author | Sterling, T.R. | |
dc.contributor.author | Leslie, A. | |
dc.contributor.author | Andrade, B.B. | |
dc.date.accessioned | 2022-08-15T20:11:09Z | |
dc.date.available | 2022-08-15T20:11:09Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12866/12030 | |
dc.description.abstract | Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses. Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. Results: PGE-M and LTE4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. Conclusion: The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia. | en_US |
dc.language.iso | eng | |
dc.publisher | Frontiers Media | |
dc.relation.ispartofseries | Frontiers in Immunology | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es | |
dc.subject | Mycobacterium tuberculosis | en_US |
dc.subject | dysglycemia | en_US |
dc.subject | anti-tuberculosis treatment | en_US |
dc.subject | lipid mediators | en_US |
dc.subject | urinary eicosanoids | en_US |
dc.title | Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis | en_US |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | https://doi.org/10.3389/fimmu.2022.919802 | |
dc.relation.issn | 1664-3224 |
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